The use of biopharmaceutic classification of drugs in drug discovery and development: current status and future extension

Abstract

Bioavailability (BA) and bioequivalence (BE) play a central role in pharmaceutical product development and BE studies are presently being conducted for New Drug Applications (NDAs) of new compounds, in supplementary NDAs for new medical indications and product line extensions, in Abbreviated New Drug Applications (ANDAs) of generic products and in applications for scale-up and post-approval changes. The Biopharmaceutics Classification System (BCS) has been developed to provide a scientific approach for classifying drug compounds based on solubility as related to dose and intestinal permeability in combination with the dissolution properties of the oral immediaterelease (IR) dosage form. The aim of the BCS is to provide a regulatory tool for replacing certain BE studies by accurate in-vitro dissolution tests. The aim of this review is to present the status of the BCS and discuss its future application in pharmaceutical product development. The future application of the BCS is most likely increasingly important when the present framework gains increased recognition, which will probably be the case if the BCS borders for certain class II and III drugs are extended. The future revision of the BCS guidelines by the regulatory agencies in communication with academic and industrial scientists is exciting and will hopefully result in an increased applicability in drug development. Finally, we emphasize the great use of the BCS as a simple tool in early drug development to determine the rate-limiting step in the oral absorption process, which has facilitated the information between different experts involved in the overall drug development process. This increased awareness of a proper biopharmaceutical characterization of new drugs may in the future result in drug molecules with a sufficiently high permeability, solubility and dissolution rate, and that will automatically increase the importance of the BCS as a regulatory tool over time.

Equilibrium solubility versus intrinsic dissolution: characterization of lamivudine, stavudine and zidovudine for BCS classification

“…Thus, it is possible to reduce time, costs and exposure of healthy volunteers to develop new medicinal products (Chen, Yu, 2009;Cook, Addicks, Wu, 2008;Lennernäs, 2007;Lennernäs, Abrahamsson, 2005;Lindenberg, Kopp, Dressman, 2004;Lobenberg, Amidon, 2000;United States, 2000).…”

“…Thereby, the drugs can be classified into four classes: class I (high solubility and high permeability), class II (low solubility and high permeability), class III (high solubility and low permeability), and class IV (low solubility and low permeability) (Amidon et al, 1995;Lennernäs, Abrahamsson, 2005;Löbenberg, Amidon, 2000; United States, 2000).…”

Polysaccharides in Oral Drug Delivery — Recent Applications and Future Perspectives

“…These class II drugs are poorly soluble but highly permeable, so an increase in dissolution rate and apparent solubility (which can increase upon CD complexation by a factor of 10 1 to 10 3 ) 30 will result in an increased amount of drug permeating through the gut wall, potentially leading to higher bioavailability 31 . Figure 5 shows the possible cyclodextrin-effects on in vitro dissolution and in vivo drug absorption of a BCS class II compound 30 .…”

“…In contrast, from hydrophilic glyburide-CD complexes obtained by complexation with methyl β-CD and HP-β-CD, the complete dose of the drug is released within a few minutes. As glyburide is a BCS class II drug, the dissolution profiles predict an increase in bioavailability when the drug would be administered as a CD complex (preferably a hydrophilic CD-complex) 27,31 .…”

Biotransformações dos terpenos ?-cariofileno e ácido 3?-acetoxi-copálico presentes em oleorresinas de Copaifera sp utilizando fungos filamentosos e bactérias do trato gastrointestinal e avaliação da atividade citotóxica dos derivados obtidos

“…A via de administração oral é a preferida para administração de fármacos, sendo que 84% dos cinquenta medicamentos mais vendidos na Europa e Estados Unidos são administrados por esta via (Lennernas et al, 2005). Todos os fármacos administrados por via oral passam pelo metabolismo hepático e pelo metabolismo bacteriano, este último ocorrendo principalmente no trato gastrointestinal inferior, se não forem totalmente absorvidos no trato gastrointestinal superior.…”